Figure 1 Endocranial Shape Differences between Neandertals and Modern Humans

Highlights

• We use fossil skull data to derive an index of endocranial shape in human MRI scans

• In 4,468 Europeans, we screen introgressed Neandertal SNPs for association with the index

• Lead SNPs consistently associate with reduced globularity in five separate subsamples

• These SNPs affect neural expression of two genes linked to neurogenesis and myelination

Summary

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1, 2, 3, 4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape.

Neandertals (Figure 1A) and modern humans (Figure 1B) have similar endocranial volumes but distinct endocranial shapes. Modern humans have a globular-shaped braincase, with a round and expanded posterior cranial fossa housing the cerebellum, and more bulging parietal bones [2, 3, 4]. Contrasting the average endocranial shapes of modern humans and Neandertals, Kochiyama et al. [5] proposed that the biggest differences between these groups are found in the cerebellum. Comparative analyses suggest rapid evolutionary changes of this brain structure in great apes and humans [8, 9]. Our analysis of endocranial shape based on data from [4] demonstrates that other regions beyond the cerebellum are relatively larger in modern humans than in Neandertals, including parts of the prefrontal cortex and the occipital and temporal lobes (Figures 1C and 1D). In contrast, parietal bulging [2, 3, 4] is not linked to an increased surface area, suggesting that the parietal lobe is “displaced” by reorganization of other—presumably subcortical—parts of the brain.